1. Field of the Invention
The present invention relates to a process for producing UCN-01 from a solution containing UCN-02 in an efficient and simple manner without complicated steps.
2. Brief Description of the Background Art
UCN-01 is a well-known compound with anti-cancer activity and anti-bacterial activity, having the structure represented by the following formula (II). ##STR1##
The following processes for producing UCN-01 are known:
(1) Japanese Published Unexamined Patent Application 87/220196 provides a fermentation method comprising culturing a microorganism of genus Streptomyces with an ability to generate UCN-01 in a culture medium and harvesting the generated UCN-01; PA0 (2) WO 89/07105 provides a method comprising three-step chemical synthesis of UCN-01 from staurosporine represented by the following formula (III). ##STR2## PA0 (3) Japanese Published Unexamined Patent Application 94/9645 provides a method comprising oxidizing staurosporine in a solution comprising dimethyl sulfoxide and an aqueous alkali solution to a racemic mixture of UCN-02 represented by the following formula (I): ##STR3##
Staurosporine is a potent inhibitor of Protein Kinase C and can be readily obtained from Streptomyces sp. Staurosporine is also commercially available, for instance, from Fermentek Corp. of Jerusalem, Israel.
and a steric isomer thereof, UCN-01 represented by the formula II above, and recovering UCN-01 by column chromatography using a carrier such as a synthetic adsorbent (for example, Diaion HP-20SS manufactured by Mitsubishi Chemical Industries, Co., Ltd.) and silica gel.
However, these methods are disadvantageous in that the culture titer by the fermentation of method (1) is low; the yield of UCN-01 resulting from the chemical synthesis of method (2) is low because 3 steps are required; and the recovery of UCN-01 is low in the column chromatography purification step of method (3) because UCN-02 must be removed as an impurity. Thus, known procedures are very complicated and are not applicable to large scale commercial synthesis.